Carbohydrates: Structure, Function, and Biological Roles

Carbohydrates: Structure, Function, and Biological Roles

Introduction to Carbohydrates

Carbohydrates, also known as saccharides, are one of the most important classes of biomolecules in biology and health. They serve as primary energy sources, structural components, and mediators of cell recognition and communication.

• Primary Energy Source: Carbohydrates are the main fuel for the body, especially for the brain and muscles. Their metabolism is central to nutrition and energy production.

• Structural Roles: Carbohydrates form key structural components in plants (e.g., cellulose) and in cells (e.g., glycoproteins, glycolipids).

• Cell Recognition and Communication: Carbohydrates on cell surfaces help cells identify and interact with each other, which is crucial for immunity and development.

• Health and Disease: Understanding carbohydrates is essential for explaining diseases such as diabetes, lactose intolerance, and obesity.

• Biotechnology and Medicine: Carbohydrates are used in vaccines, drug design, and biomaterials.

Carbohydrate and Sugar Structure

Classification and Nomenclature

Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis. Their general formula is $(C_nH_{2n}O_n)$, where $n \geq 3$.

• Monosaccharides: Single sugar units (e.g., glucose, fructose).

• Oligosaccharides: Short chains of monosaccharide units (typically 2–10), often attached to proteins (glycoproteins) or lipids (glycolipids).

• Polysaccharides: Long chains of monosaccharide units (e.g., cellulose, glycogen).

Monosaccharides (D-aldoses)

Monosaccharides are classified by the number of carbon atoms and the type of carbonyl group present:

• Aldoses: Contain an aldehyde group.

• Ketoses: Contain a ketone group.

• Triose, Tetrose, Pentose, Hexose: Indicate 3, 4, 5, or 6 carbon atoms, respectively.

The number of possible stereoisomers for a monosaccharide with $n$ chiral centers is $2^n$.

Fischer Convention

The Fischer convention is used to denote the configuration of monosaccharides. The D- and L- designations are based on the configuration of D- and L-glyceraldehyde. Epimers are sugars that differ in configuration around only one specific carbon atom.

• Example: D-glucose and D-mannose are epimers at C-2.

Monosaccharides Form Rings

Ring Formation

Monosaccharides with five or more carbons typically exist in cyclic (ring) forms in solution. The ring forms are created by the reaction of a carbonyl group with a hydroxyl group, forming a hemiacetal (from an aldehyde) or hemiketal (from a ketone).

• Furanose: Five-membered ring structure.

• Pyranose: Six-membered ring structure.

Projections and Anomeric Forms

Sugars can be represented in different projections (Fischer, Haworth, chair conformations). Cyclization creates a new chiral center at the anomeric carbon, resulting in two anomers: alpha (α) and beta (β).

• Alpha (α): The OH on the anomeric carbon is trans to the CH2OH group.

• Beta (β): The OH on the anomeric carbon is cis to the CH2OH group.

Sugar Modifications

Common Modifications

• Oxidation:

  • Aldose aldehyde to carboxylic acid → aldonic acid (e.g., D-gluconic acid).

  • Primary alcohol of aldoses to uronic acid → uronic acid (e.g., D-glucuronic acid).

• Reduction: Aldoses and ketoses can be reduced to yield polyhydroxy alcohols (alditols), e.g., ribitol, xylitol, glycerol.

• Deoxy Sugars: Replacement of an OH group by H (e.g., 2-deoxyribose in DNA).

• Amino Sugars: Replacement of an OH group by an amino group, sometimes acetylated (e.g., N-acetylglucosamine, N-acetylgalactosamine).

• Sialic Acids: Glycoproteins may contain N-acetylneuraminic acid (a sialic acid) derived from N-acetylmannosamine and pyruvic acid.

Glycosidic Bonds

Formation and Types

Glycosidic bonds link two monosaccharides via an oxygen atom. The bond can be in the α or β configuration and can occur at various positions (e.g., 1→2, 1→4, 1→6).

• Example: Maltose is linked by an α(1→4) glycosidic bond; cellobiose by a β(1→4) bond.

Glycosidic bonds also attach sugars to nucleotides (as in DNA and RNA), and these bonds hydrolyze very slowly.

Disaccharides and Polysaccharides

• Disaccharides: Sucrose, lactose, maltose, cellobiose, isomaltose, trehalose, etc.

• Cellulose: β(1→4) linkage of glucose units; forms rigid plant cell walls.

• Starch (Amylose): α(1→4) linkage of glucose; digestible by humans.

• Amylopectin: Contains both α(1→4) and α(1→6) linkages (branched structure).

Modified Sugar Peptides and Structural Polysaccharides

Chitin

Chitin is a structural polysaccharide found in the exoskeletons of insects, crustaceans, and in fungal cell walls. It is composed of N-acetylglucosamine units linked by β(1→4) bonds.

Other Modified Sugars

Various modified sugars (e.g., dermatan sulfate, keratan sulfate, chondroitin sulfate, heparin) are found in connective tissues and extracellular matrices.

Bacterial Films and Peptidoglycans

Bacterial biofilms are composed of highly hydrated polysaccharides that protect bacteria and create barriers to antibiotics. Bacterial cell walls are made of peptidoglycans, which include unique amino acids (often D-amino acids) that prevent degradation by proteases.

Proteoglycans

Proteoglycans are large complexes of proteins and glycosaminoglycans (GAGs) that resemble a bottle brush. They have a core protein with both O-linked and N-linked oligosaccharides, and a central strand of hyaluronate. These structures are important in connective tissues and extracellular matrices.

Eukaryotic Glycoproteins

N-linked and O-linked Oligosaccharides

Eukaryotic glycoproteins can have oligosaccharides attached via the nitrogen atom of asparagine (N-linked) or the oxygen atom of serine/threonine (O-linked). N-linked oligosaccharides have a pentasaccharide core that repeats and are synthesized in a stepwise manner.

Functions of Oligosaccharides

• Define protein structure by occupying large volumes and influencing protein folding.

• Mediate recognition events (e.g., blood group antigens, cell-cell interactions).

Glycocalyx and Cell Recognition

The glycocalyx is a carbohydrate-rich layer on the surface of cells, especially red blood cells. Oligosaccharides in the glycocalyx mediate recognition events and can be highly variable, allowing for numerous recognition possibilities.

Lectins

Lectins are proteins on cell surfaces that bind specific carbohydrate structures. For example, selectins attach leukocytes to endothelial cells during immune responses. Human galectin-2 binds β-galactosides like lactose via hydrogen bonds.

Oligosaccharides as Antigenic Determinants

Oligosaccharides determine blood group antigens (ABO system):

Type	Antigen Structure
O (H antigen)	Galβ1-4GlcNAcβ1-3Galβ1-4Glc
A	H antigen + GalNAc (N-acetylgalactosamine)
B	H antigen + Gal (galactose)

Type O is the universal donor because it lacks additional terminal sugars.

Ricin: A Deadly Lectin

Ricin is a ribosome-inactivating protein composed of two subunits (A and B). The B subunit is a lectin that binds galactose and N-acetylgalactose on cell surfaces, facilitating entry. The A subunit enzymatically cleaves the N-glycosidic bond of a specific adenine in the 28S rRNA of the 60S ribosomal subunit, halting protein synthesis. Ricin is extremely toxic, with an LD50 of 0.000022 g/kg body weight (1.8 mg can be lethal to an adult).

• Mechanism: Ricin is internalized by endocytosis, trafficked to the ER, and the A subunit is released to inactivate ribosomes.

• Barley contains the A subunit but not the B, so it is not toxic.